US4755601A - Nonyl prenyl-N heterocyclics - Google Patents

Nonyl prenyl-N heterocyclics Download PDF

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Publication number
US4755601A
US4755601A US06/256,579 US25657981A US4755601A US 4755601 A US4755601 A US 4755601A US 25657981 A US25657981 A US 25657981A US 4755601 A US4755601 A US 4755601A
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United States
Prior art keywords
interferon
virus
acid
sub
solution
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Expired - Fee Related
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US06/256,579
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English (en)
Inventor
Yoshiyuki Tahara
Hiroyasu Koyama
Yasuhiro Komatsu
Reiko Kubota
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Nisshin Seifun Group Inc
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Nisshin Seifun Group Inc
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Assigned to NISSHIN FLOUR MILLING CO., LTD. reassignment NISSHIN FLOUR MILLING CO., LTD. ASSIGNMENT OF ASSIGNORS INTEREST. Assignors: KOMATSU YASUHIRO, KOYAMA HIROYASU, KUBOTA REIKO, TAHARA YOSHIYUKI, TAKAHASHI TOSHIHIRO
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
    • C07D295/027—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring
    • C07D295/03—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring with the ring nitrogen atoms directly attached to acyclic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/04—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain

Definitions

  • This invention relates to new nonaprenylamine derivatives and the acid addition salts thereof, which are useful for controlling virus infection of vertebrate animals.
  • Antivirotics reported so far include interferon, substances capable of inducing interferon, i.e. inducers (interferon inducers), amantadine hydrochloride or synthetic substances, such as methysazone, which directly exert inhibitory effect on the virus propagation.
  • Interferon is glycoprotein having antiviral and antitumor activity, said glycoprotein being produced in situ by cells of a vertebrate animal when the cells are infected with virus, and is effective against very wide range of virus-infected diseases.
  • Known inducers which induce interferon in vertebrate animals by a process other than the virus infection, include natural high molecular substances such as double chain ribonucleic acid of bacteriophage of a certain species, or synthetic high molecular substances such as double chain ribonucleic acid, typical of which is polyinosinic acid-polycytidylic acid, or low molecular inducers such as tyrolone.
  • the present inventors extensively conducted studies in finding compounds capable of producing interferon of high potency and, moreover, having antiviral activity on the biological level, and as the result they have eventually found new nonaprenylamine derivatives of the following general formula (I) and acid addition salts thereof, which show excellent interferon inducing ability and, at the same time, demonstrate excellent antiviral and antitumor activity even in the biological test, and which are thus expected as a medicament.
  • New nonaprenylamine derivatives of this invention are represented by the following general formula ##STR1## wherein R is an atomic grouping capable of forming together with the adjacent nitrogen atom a 5- or 6-membered heterocyclic ring, which may contain an additional hetero atom, said R optionally being substituted with a hydrogen atom or a hydroxy lower alkyl group, provided that said additional hetero atom is a nitrogen atom.
  • nonaprenylamine derivative of this invention represented by the above-mentioned general formula (I) and acid addition salts thereof, there may be adopted a process in which the known procedures for the amine synthesis are applied to the starting nonaprenol (solanesol) represented by the formula ##STR2## to produce a corresponding amine derivative.
  • a desired amine may be produced according to a process which comprises converting nonaprenol of the aforesaid general formula (II) into a corresponding halide (e.g. solanesyl bromide) or aryl sulfonic acid ester (e.g. solanesyltosylate), followed by reaction with a heterocyclic derivative having at least one secondary amino group in the presence or absence of a base to produce the desired amine derivatives.
  • a corresponding halide e.g. solanesyl bromide
  • aryl sulfonic acid ester e.g. solanesyltosylate
  • An acid addition salt of the amine derivative thus obtained can be obtained by mixing said amine in an appropriate solvent with a desired acid to form a salt and crystallizing the salt out of the solution by evaporation or other means to recover the same.
  • the acid addition salts suitable for use as medicines include, for example, those with hydrochloric acid, acetic acid, citric acid, fumaric acid, lactic acid and the like.
  • Example 1 The same procedures as in Example 1 were carried out for the reaction of solanesyl bromide with a heterocyclic derivative having secondary amino group thereby to produce the below-indicated compounds, the structural formula, molecular formula, melting point and elementary analysis of which also are listed in Table 1.
  • Each test compound suspended in water with a surfactant was intraperitoneally administered to each group consisting of 5 ICR female mice weighing about 25 g. Twenty hours after administration, blood was collected from the mice and serum was separated therefrom to obtain a serum interferon. The following steps were taken in order to determine potency of the serum interferon thus induced.
  • L-929 cells derived from mice and incubated previously in a monolayer was brought into contact with the test serum solution diluted 10 times, incubated overnight at 37° C. in an incubator placed in carbon dioxide atmosphere and the dilute test serum solution was removed therefrom. Thereafter, the cells were inoculated with vesicular stomatitis virus and placed on a tissue culture medium containing 1% agar. After incubation at 37° C.
  • the cells were dyed with neutral red solution diluted to an appropriate concentration to count the number of plaques formed thereon and thereby to calculate the plaque inhibition rate in each of the test groups against a group to which no test compound had been administered.
  • the plaque inhibition rate of each test compound is shown in Table 2.
  • mice each consisting of 10 ICR female mice weighing about 15 g., were intravenously injected with 0.1 ml of a vaccinia virus (DIE strain) dilution through the vein of tail at the distance of 2 cm from the root of the tail.
  • DIE strain a vaccinia virus
  • the number of lesions in form of small pocks on the tail surface was counted after dyeing the tail with a solution containing 1% fluorescein and 0.5% methylene blue.
  • each test compound was administered intraperitoneally to the mice on the day just before inoculation of the virus, whereby antivirus activity of the test compound was evaluated in terms of inhibition of tail lesions as calculated in each test group against a group to which no test compound had been administered.
  • mice each consisting of 10 ICR female mice weighing about 25 g. were challenged by intralation of neblyzed influenza virus A/PR-8.
  • a solution of each test compound in an aqueous solution containing a surfactant was intraperitoneally administered to the mice 24 hours and 3 hours before the virus infection, and 5 times every other day from the second day after the infection.
  • the mice that survived 21 days after the challenge were regarded as survivors, and survival rate was obtained according to the following equation. ##EQU1##
  • the active ingredients of the present invention are used for prevention and treatment of virus-infected diseases, they are administered to patients by such techniques involving oral, inhalant, or the like administration as well as subcutaneous, intramascular and intravenous injection.
  • the active ingredient of the present invention is used in a dose of 0.5-20 mg/kg, preferably 3-5 mg/kg several times (2-4 times) per day.
  • compositions for medication for example, tablets, capsules, granules, powder, liquid preparation for oral use, eye lotions, suppositories, ointments, injections and the like, according to any conventional method.
  • the present active ingredients When the present active ingredients are orally administered, they may be formulated into tablets, capsules, granules or powder.
  • These solid preparations for oral use may contain commonly used excipients, for example, silicic anhydride, metasilicic acid, magnesium alginate, synthetic aluminum silicate, lactose, cane sugar, corn starch, microcrystalline cellulose, hydroxypropylated starch or glycine, and the like; binders, for example, gum arabic, gelatin, tragacanth, hydroxypropyl cellulose or polyvinylpyrrolidone; lubricants, for example, magnesium stearate, talc or silica; disintegrating agents, for example, potato starch and calcium carboxymethyl cellulose; or wetting agents, for example, polyethylene glycol, sorbitan monooleate, polyoxyethylene-hardened castor oil, sodium laurylsulfate.
  • excipients for example, silicic anhydride, metasilicic acid, magnesium al
  • the present active ingredients may be formulated by dissolving or suspending them in polyethylene glycol or commonly used oily substrates such as sesame oil, peanut oil, germ oil, fractionated coconut oil such as Miglyol®, or the like. Tablet or granule preparations may be coated according to the usual method.
  • Liquid preparation for oral use may be in the form of aqueous or oily emulsion or syrup, or alternatively in the form of dry product which can be re-dissolved before use by means of a suitable vehicle.
  • emulsifying aids such as sorbitol syrup, methyl cellulose, gelatin, hydroxyethyl cellulose and the like
  • emulsifiers for example, lecithin, sorbitan monooleate, polyoxyethylene-hardened castor oil, non-aqueous vehicles, for example, fractionated coconut oil, almond oil, peanut oil and the like
  • antiseptics for example methyl p-hydroxybenzoate, propyl p-hydroxybenzoate or sorbic acid.
  • these preparations for oral use may contain, if necessary, preservatives, stabilizers and the like additives.
  • the present active ingredients are administered in the form of non-oral suppository, they may be formulated according to the ordinary method using oleophilic substrates such as cacao oil or Witepsol®, or may be used in the form of rectum capsule obtained by wrapping a mixture of polyethylene glycol, sesame oil, peanut oil, germ oil, fractionated coconut oil and the like in a gelatin sheet. The rectum capsule may be coated, if necessary, with waxy materials.
  • the present active ingredients When used in the form of injection, they may be formulated into preparations of oil solution, emulsified solution or aqueous solution, and these solutions may contain commonly used emulsifiers, stabilizers or the like additives.
  • compositions can contain the present active ingredients in an amount of at least 1%, preferably 5 to 50%.
  • a mixture of 25 g. of N- ⁇ -hydroxyethyl-N'-solanesylpiperazine and 7.5 g. of polyoxyethylene castor oil in acetone was mixed with 25 g. of silicic anhydride. After evaporation of the acetone, the mixture was mixed further with 5 g. of calcium carboxymethylcellulose, 5 g. of corn starch, 7.5 g. of hydroxypropylcellulose and 20 g. of microcrystalline cellulose, and 30 ml of water was added thereto and kneaded to give a granular mass. The mass was pelletized by means of a pelletizer (ECK pelletter of Fuji Paudal Co., Japan) equipped with No.
  • a homogeneous solution was prepared by mixing 50 g. of N-solanesylpiperazine dihydrochloride with 130 g. of polyethylene glycol (Macrogol 400).
  • a gelatin solution was prepared which contained 93 g. of gelatin, 19 g. of glycerine, 10 g. of D-sorbitol 0.4 g. of ethyl p-hydroxybenzoate, 0.2 g. of propyl p-hydroxybenzoate and 0.4 g. of titanium oxide and which was used as a capsule film forming agent.
  • the previously obtained solution, together with the capsule film forming agent, was treated with a manual type flat punching machine to obtain soft capsules each having the contents of 180 mg.
  • a mixture of 5 g. of N- ⁇ -hydroxyethyl-N'-solanesylpiperazine, an appropriate amount of peanut oil and 1 g. of benzyl alcohol was made a total volume of 100 cc by addition of peanut oil.
  • the solution was portionwise poured in an amount of 1 cc under asepsis operation into an ampule which was then sealed.
  • Nikkol HCO-60 a tradename

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Virology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
US06/256,579 1980-04-23 1981-04-22 Nonyl prenyl-N heterocyclics Expired - Fee Related US4755601A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP5510880A JPS56150068A (en) 1980-04-23 1980-04-23 Nonaprenylamine derivative
JP55-55108 1980-04-23

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US07/178,510 Division US4857529A (en) 1980-04-23 1988-04-07 Interferon inducing, anti-vaccinia, and/or anti-influenza compositions

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US4755601A true US4755601A (en) 1988-07-05

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US06/256,579 Expired - Fee Related US4755601A (en) 1980-04-23 1981-04-22 Nonyl prenyl-N heterocyclics
US07/178,510 Expired - Fee Related US4857529A (en) 1980-04-23 1988-04-07 Interferon inducing, anti-vaccinia, and/or anti-influenza compositions

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US (2) US4755601A (enrdf_load_stackoverflow)
JP (1) JPS56150068A (enrdf_load_stackoverflow)
CA (1) CA1183136A (enrdf_load_stackoverflow)
DE (1) DE3116250A1 (enrdf_load_stackoverflow)
FR (1) FR2481281A1 (enrdf_load_stackoverflow)
GB (1) GB2076395B (enrdf_load_stackoverflow)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4857529A (en) * 1980-04-23 1989-08-15 Nisshin Flour Milling Co., Ltd. Interferon inducing, anti-vaccinia, and/or anti-influenza compositions
US10927084B2 (en) 2017-01-26 2021-02-23 Tosoh Corporation Alkanolamine, friction-reducing agent, and lubricating oil composition

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4468458A (en) * 1980-01-12 1984-08-28 Eisai Co., Ltd. Two-functional-group-containing terpenoids, processes for the preparation of the same, and anti-ulcer agents containing the same
WO1998025617A1 (en) * 1996-12-13 1998-06-18 Merck & Co., Inc. Substituted aryl piperazines as modulators of chemokine receptor activity

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US2590126A (en) * 1948-03-10 1952-03-25 Searle & Co Quaternary ammonium salts of 2, 6-lupetidine
US2706195A (en) * 1952-06-26 1955-04-12 Rohm & Haas Bis(5, 5, 7, 7-tetramethyl-2-octenyl) dialkylammonium salts
US3232949A (en) * 1961-10-12 1966-02-01 Eastman Kodak Co Process of manufacturing branchedchain mono-olefinic aliphatic acids and intermediates therefor
US3268524A (en) * 1961-02-20 1966-08-23 Cumberland Chemical Corp Process for the preparation of amines of the acetylenic series
US3268583A (en) * 1961-02-20 1966-08-23 Cumberland Chemical Corp Acetylenic amides
US4221810A (en) * 1978-03-23 1980-09-09 Nisshin Flour Milling Co., Ltd. Antiulcer compounds
US4265910A (en) * 1979-05-04 1981-05-05 Nisshin Flour Milling Co., Ltd. Isoprenylamines
GB2065109A (en) * 1979-11-19 1981-06-24 Nisshin Flour Milling Co Decaprenylamine derivatives
GB2079395A (en) * 1980-06-27 1982-01-20 British Aluminium Co Ltd Clamp joint for panels
US4324916A (en) * 1979-11-19 1982-04-13 Nisshin Flour Milling Co. Ltd. Decaprenylamine derivatives

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US4271810A (en) * 1980-01-11 1981-06-09 General Motors Corporation Divided chamber engine with prechamber exhaust recirculation
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US2590126A (en) * 1948-03-10 1952-03-25 Searle & Co Quaternary ammonium salts of 2, 6-lupetidine
US2706195A (en) * 1952-06-26 1955-04-12 Rohm & Haas Bis(5, 5, 7, 7-tetramethyl-2-octenyl) dialkylammonium salts
US3268524A (en) * 1961-02-20 1966-08-23 Cumberland Chemical Corp Process for the preparation of amines of the acetylenic series
US3268583A (en) * 1961-02-20 1966-08-23 Cumberland Chemical Corp Acetylenic amides
US3232949A (en) * 1961-10-12 1966-02-01 Eastman Kodak Co Process of manufacturing branchedchain mono-olefinic aliphatic acids and intermediates therefor
US4221810A (en) * 1978-03-23 1980-09-09 Nisshin Flour Milling Co., Ltd. Antiulcer compounds
US4265910A (en) * 1979-05-04 1981-05-05 Nisshin Flour Milling Co., Ltd. Isoprenylamines
GB2065109A (en) * 1979-11-19 1981-06-24 Nisshin Flour Milling Co Decaprenylamine derivatives
US4324916A (en) * 1979-11-19 1982-04-13 Nisshin Flour Milling Co. Ltd. Decaprenylamine derivatives
GB2079395A (en) * 1980-06-27 1982-01-20 British Aluminium Co Ltd Clamp joint for panels

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Tahara et al., "Anti-Ulcer Fatty Acid Esters," Chem Abst. 92: 198,583 (1979).
Tahara et al., "Anti-Ulcer Polyprenyl Alcohols"; Chem. Abst. 92: 129133z (1979).
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Tahara et al., . . . Decaprenylacetic Acid Derivatives . . . Chem Abst. 92: 111189. *
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4857529A (en) * 1980-04-23 1989-08-15 Nisshin Flour Milling Co., Ltd. Interferon inducing, anti-vaccinia, and/or anti-influenza compositions
US10927084B2 (en) 2017-01-26 2021-02-23 Tosoh Corporation Alkanolamine, friction-reducing agent, and lubricating oil composition

Also Published As

Publication number Publication date
JPS56150068A (en) 1981-11-20
FR2481281A1 (fr) 1981-10-30
DE3116250A1 (de) 1982-04-01
DE3116250C2 (enrdf_load_stackoverflow) 1988-12-22
GB2076395B (en) 1984-03-07
FR2481281B1 (enrdf_load_stackoverflow) 1984-02-17
JPH0132826B2 (enrdf_load_stackoverflow) 1989-07-10
US4857529A (en) 1989-08-15
GB2076395A (en) 1981-12-02
CA1183136A (en) 1985-02-26

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